Individual assessment and classification of complex diseases by a data-based clinical disease profile

ABSTRACT

An tool and method is disclosed to assess disease activity and to classify complex diseases using basic clinical data. The tools and methods allow identifying and consulting affected individuals based on comprehensive bedside examinations and thus provide a basis for the personalized management of complex diseases.

CROSS REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. provisional application60/744,460, filed Apr. 7, 2006, which is incorporated by reference inits entirety.

FIELD OF THE INVENTION

The invention relates to assessment tools, including a systems and/orcomputer programs and methods for identifying, calculating andindicating a score associated with a disease for an individual or apopulation based on clinical data such as selected sets of measurableindicator variables and/or parameters obtained by physicians. The toolsand methods may be employed to assess the state of one or more diseasesin an individual or in a population, in the present and/or in thefuture,

BACKGROUND OF THE INVENTION

Chronic complex diseases are wide spread and their occurrence has beensurging worldwide with an aging and an increasingly sedentarypopulation. One of these complex diseases, namely arteriosclerosis, is acommon cause of severe diseases such coronary heart disease (1). Toprevent deaths and disabilities, it is important to identify individualsat risk, e.g, in the case of arteriosclerosis, at risk to developcardiovascular events (2, 3). Several risk factor scoring systems havebeen developed for this purpose (4, 5). These scoring systems haveseveral limitations (6). First, they contain a temporal and spatialbias: the baseline data from which the score formulas are derived wereusually collected in the past, sometimes decades ago, and theindividuals participating in the study cohort live in certain regions ofthe world. Thus, general lifestyle changes within a population which canoccur over a short period of time and may have a strong impact on therisk factors for arteriosclerosis (7), are not being considered. Manydiseases, including arteriosclerosis, are also affected by the geneticbackground which varies in populations from different continents (8).Second, most risk score calculations for diseases such asarteriosclerosis end at an age of 65 to 70 years because, e.g.,cardiovascular events are highly prevalent in this age group. For thisage group, the probability to develop cardiovascular events within thenext 10 years is 50%, but drugs used to prevent such events have to betaken infinitely and their side effects are particularly common in theelderly (9, 10). Evidence-based guidelines to treat common disorderssuch as cardiovascular disease, osteoporosis or diabetes with amultitude of drugs have recently been discussed in the light of theincreasing number of patients with more than one of these conditions(11). In order to avoid unnecessary or even harmful multidrug regimens,it is of great importance to allocate treatment precisely to thepatients who need it and not to the general population above 70. Third,patients with cardiovascular risk factors (e.g. arterial hypertension,hyperlipidemia or diabetes), e.g., for arteriosclerosis are treated forthem: they take antihypertensive, cholesterol or glucose lowering drugs,which all potentially affect the variables entering the predictionalgorithm and therefore may influence the estimation of the currentrisk. Since some of these regimens (e.g. statins or angiotensinconverting enzyme inhibitors (12, 13)) have beneficial effects onimportant pathogenic steps of symptomatic arteriosclerosis and may evenrevert arteriosclerotic lesions, the question arises whether andparticularly when these treatments could be discontinued.

The publications and other materials, including patents, used herein toillustrate the invention and, in particular, to provide additionaldetails respecting the practice are incorporated herein by reference intheir entirety. For convenience, the publications are referenced in thistext by numerals corresponding to those in the appended bibliography.

Thus, there is a need for accurate assessment of current diseaseactivity for the individual patient to replace or supplement riskprediction tools which are based on probabilities rather than facts.Particularly in view of the fact that complex disease, such ascardiovascular disease, are emerging in less developed countries (14)where accessibility to, e.g., coronary catheterization or other modernvascular imaging facilities is limited, this assessment shouldpreferably be based on data obtained, at least in part, from the patientin a concise, short and affordable examination.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1. The Data-based clinical disease profile and the Disease activityscore.

The statistical comparison of more than 70 clinical parameters betweenpatients with proven symptomatic arteriosclerosis and patients withoutcardiovascular events in the past revealed 25 numerical variables thatwere different between the two groups. The range of the complete datasetfor the symptomatic patients is shown, visually weighed and color coded:lighter gray shading (or green color) represents the quartile closest tothe asymptomatic patients, light gray shading (or yellow color) thesecond, dark gray shading (or orange color) the third quartile anddarker gray shading (or red color) the quartile most distant to theasymptomatic patients. This quartile distribution is the basis for theassignment of the individual data-based clinical disease profile and forthe calculation of the disease activity score for the individual patientaccording, in this case, to the following formula: disease activityscore=Σ[α₁+α₂+α₃+ . . . +α₂₅]/(25-[missing variables].

FIG. 2. Reproducibility of the clinical assessment and of the diseaseactivity score.

A. The numerical variables which were collected by differentinvestigators during two different time periods were compared and showan ideal linear correlation. B. The quartile distribution of the diseaseactivity score is nearly identical for the two study periods confirmingthe consistency and reliability of the method to establish a data-basedclinical disease profile.

FIG. 3. Alignment of the data-based clinical disease profiles into anarray format.

The clinical data arrays are grouped in four quadrants according to theabsence or presence of cardiovascular events in the past (left and rightpanel, respectively) and according to the gender (upper and lower panel,respectively). M=patients with metabolic syndrome. BMI=body mass index.SBP=systolic blood pressure. ABI=ankle brachial index. BSR=bloodsedimentation rate.

FIG. 4. The disease activity score correlates with prognosis andseverity of arteriosclerosis.

A. The 10 year risk to develop cardiovascular events was calculatedusing the Framingham algorithm (18) and could be shown to be correlatedwith the disease activity score. B. The disease activity score (medianand interquartile range are represented as columns with error bars;maximum and minimum values as circles) are shown for three patientsgroups: the first including patients without cardiovascular events(n=110), the second including patients with a cardiovascular event at asingle site (n=72) and the third including patients with cardiovascularevents affecting more than one organ (n=28).

FIG. 5. The disease activity score correlates with age.

FIGS. 6-1 and 6-2. The phenotypical correlation plot of asymptomatic andsymptomatic arteriosclerosis.

The 61 clinical datasets for which more than 75% of the data wereavailable were correlated and the linear regression coefficient Rcalculated. 6-1. Patients without cardiovascular events. 6-2. Patientswith symptomatic arteriosclerosis. R-values are shown. If gray scalecoded, the figure legend assigns R-values to certain gray scales.

FIG. 7. Symptomatic arteriosclerosis is linked with osteoporosis.

In patients with symptomatic arteriosclerosis but not in patientswithout cardiovascular events, the body size decreases with age (A) andis negatively correlated with systolic blood pressure (B).

FIG. 8. Receiver operating characteristic (ROC) curve for the diseaseactivity score (A) and the number of risk factors (B). Area under thecurve is shown within the graph.

FIG. 9. ROC curve for the Framingham score.

FIG. 10. Comparison of the disease activity score over time for a groupof individuals without the disease (left) and a group of individualswith the disease (right).

SUMMARY OF THE INVENTION

The present invention is directed towards an assessment tool for adisease comprising:

(a) a first set of data recorder said first set of data comprising dataof measurable indicator parameters and/or variables collected from afirst group of individuals having said disease;(b) a second set of data recorder, said second set of data comprisingdata of said measurable indicator parameters and/or variables in (a),but collected from a second group of individuals without said disease;(c) a comparing unit/function which compares said first set of data withsaid second set of data; and(d) a selecting unit/function which selects a profiling set from saidmeasurable indicator parameters and/or variables, wherein a coding, suchas color, shade or value coding, attributed to each of said measurableparameters and/or variables of said profiling set reflects a diseaseactivity measured by said measurable parameters and/or variables.

Said coding may contribute to a data-based clinical disease profileand/or an activity score of said disease. Said selecting unit/functionor a further selecting unit/function may select a correlation set,wherein said coding may correlate at least two different of saidmeasurable indicator parameters and/or variables of the correlation set.

An attribution unit/function may calculate the percentile distributionof each measurable indicator parameter and/or variable of said profilingset of said first and/or second group, wherein said coding reflects thispercentile distribution.

The coding may be based on percentile ranges such as, but not limitedto, tertile, quartile, quintile, sextile, septile, octile or nonileranges of said percentile distribution.

The selecting unit/function may select said profiling set fromparameters and/or variables having a P-value of less than 0.5,preferably less than 0.4, more preferably less than 0.3, even morepreferably less than 0.2, even more preferably less than 0.1, 0.05,0.025, 0.01, 0.005, 0.0025 or 0.001 in a statistical test comparing twogroups such as, but not limited to, the Mann Whitney U test, the studentt-test, or the X² test when compared in (c).

The invention is also directed towards a method for determiningmeasurable parameters and/or variables correlated to a condition and/ordisease comprising:

(a) compiling measurable indicator parameters and/or variables;(b) collecting and/or storing a first set of data for each of saidmeasurable parameters and/or variables collected from a first group ofindividuals having said disease;(c) collecting and/or storing a second set of data for each of saidmeasurable parameters and/or variables collected from a second group ofindividuals without said disease,

wherein said individuals of (b) and (c) are selected from the samepopulation and, optionally, the first and second set of data werecollected approximately within the last 5 years, 4 years, 3 years, 2years, 1 year, 9 months, 6 months, 3 months, 2 months, 1 months, 2weeks, 1 week, 5 days, 2 days or 24 hours;

(d) selecting a profiling set from said measurable parameters and/orvariables; and(e) optionally, selecting a correlating set from said measurableparameters and/or variables.

The method may further comprise assigning said measurable indicatorparameters and/or variables a coding, such as a color, shade or valuecoding, wherein said coding may reflect a disease activity measured bythe measurable parameters and/or variables to the disease and/orcondition. The method may also comprise calculating a percentiledistribution of each measurable indicator parameter and/or variable ofsaid profiling set and/or correlation set, wherein said coding mayreflect this percentile distribution for said first and/or second group.The coding may be based on certain percentile ranges such as, but notlimited to, tertile, quartile, quintile sextile, septile, octile ornonile ranges of said percentile distribution.

The invention is also directed towards determining an activity score forat least one condition and/or disease in an individual and/or in apopulation comprising

measuring the measurable indictor parameters and/or variables of theprofiling set in said individual; anddetermining the activity score of said disease in said individual or apopulation from an average of the sum of said coding.

The invention is also directed to uses of any embodiment of theinvention.

DETAILED DESCRIPTION OF VARIOUS AND PREFERRED EMBODIMENTS OF THEINVENTION

The article “a” in the context of the present invention means one ormore unless otherwise specified.

A disease according to the present invention is any condition that, whenmanifested in an individual including non-human animals and humans suchas patients, can be associated with a set of parameters and/or variablesthat are measurable and are indicative of said condition or disease(hereinafter “measurable indicator parameters and/or variables”).Variables are numerical, while parameters comprise non-numericalclinical data. (see, “Sapira's Art & Science of bedside diagnosis”.Second Edition, Jane M. Orient. Lippincott Williams & Wilkins. 2000). Ina preferred embodiment the disease is a common, complex condition ordiseases for which a clear clinical definition exists, such as, but notlimited to, a definition provided by the World Health Organization(WHO). An individual is said to have a disease if the individual couldbe diagnosed with the disease according to such a clear clinicaldefinition. An individual I said to be without a disease if eitherhis/her history or an examination does not indicate that the individualhas the disease.

A disease activity according to the present invention is a quantifiablemeasurement of disease ranging from no disease activity (=0) to maximaldisease activity (=m, wherein m is the maximum activity value assignedto a disease).

An assessment tool according to the present invention is any system,e.g., a computer system, or an array of functions, such as a computerprogram, which is associated with a physical structure such as, but notlimited to, a server, a CD, DVD or similar. The tool may be madeavailable to clients, such as, but not limited to, hospitals,teleconsultants or the end user, via the internet. In a preferredembodiment, the assessment tool and methods of the invention allow forconsideration of environmental changes that occur or have occurred,e.g., in a population in the assessment of a disease. This means, theassessment may be performed based on data that was collected proximateto its use and/or within the relevant population. Thus, in a preferredembodiment of the invention, the data for a standard reference, iscollected within the time frame of less than two years, less than oneyear, less than six month, less than 3 month, or less than one month oreven less than a fortnight from its use, e.g., as part of the assessmenttool of the present invention. Accordingly, the standard reference mightstem from a contemporary cohort of, e.g., individuals with or withoutthe disease or set of diseases in question.

A recorder is, in the context of the present invention any collectingand/or storing unit or function. A recorder may collect and/or stores asets of data (a set of data recorder), such as measurable indicatorparameters and/or variables, pertaining to, e.g., a particular diseaseor a variety of diseases. In a preferred embodiment, the recorder storesmeasurable indicator parameters and/or variables that have beencollected from individuals. As the person skilled in the art willappreciate, a wide variety of options exists how data such as such a setof data can be collected and stored all of which form part of thepresent invention. In one embodiment, the recorder is a centralprocessing unit of a PC or a server. The recorder can also take the formof a function that is associated with, including embedded in, a physicalstructure such as, but not limited to, a CD, DVD or other, e.g., storingdevice. The term unit/function, e.g. a selecting or comparingunit/function, similarly indicates that selecting and/or comparing canbe taken over by a distinct physical entity, but can also just be afunction associated with a distinct physical structure such as, but notlimited to, a CD, DVD or other, e.g., storing device. The measurableindicator parameters and/or variables are preferably readily assessableones, e.g., via bedside examination and/or a number of laboratory tests.Thus, they can be assessed in facilities lacking sophisticatedequipment, such as expensive imaging equipment. For example, theindicator parameters and/or variables may be assessed in a mobile ortemporary facility. As the person skilled in the art will appreciate,the measurable indicator parameters and/or variables vary to differentdegrees from disease to disease. The questionnaire in Appendix I as wellas the Table in Appendix II provide convenient tools to ascertain theseparameters and/or variables for a wide variety of diseases. However, itis well within the skill of the artisan to modify a questionnaire and/ortable of this kind. Also, it might be desirable to adjust such aquestionnaire and/or table to take into consideration the specifics of,e.g., a population, location or time in which/where/when the assessmentis performed.

A profiling set is a collection of measurable indicator parametersand/or variables from a relevant number of individuals that forms thebasis to profile a certain disease, e.g., arteriosclerosis. A profilingset will comprise at least a majority (more than 50%) of measurableindicator parameters and/or variables that can be clearly linked to aparticular disease, e.g. by establishing statistically significantdifferences between individuals having a disease and individuals withoutthe disease and selecting those that showed such differences between thetwo groups. Thus, in a preferred embodiment of the invention, theprofiling set comprises, consists of or essentially consists of a set ofparameters and/or variables having a P-value of less than 0.5,preferably less than 0.4, more preferably less than 0.3, even morepreferably less than 0.2, even more preferably less than 0.1, 0.05,0.025, 0.01, 0.005, 0.0025 or 0.001 in a statistical test comparing twogroups such as, but not limited to, the Mann Whitney U test, the studentt-test, or the X² test, wherein this set is a subset ofparameters/variables selected after comparing parameters/variables of afirst group of individuals having the disease and a second group nothaving the disease.

A data-based clinical disease profile according to the present inventionprofiles a disease in an individual employing a profiling set. Itcomprises, consists of or essentially consists of measurable indicatorparameters and/or variables that have been attributed a coding whichrelates the value measured for this parameters and/or variables to areference value, such as the average value measured for this parameterand/or variable in a relevant number of individuals having the diseaseor, alternatively, in a relevant number of individuals not having thedisease. These groups of individuals are also referred to herein asreference or standard reference. In one embodiment the referenceconsists of or consists essentially of individuals having the disease.

A disease activity score according to the present invention is anaverage of the measurable indicator parameters and/or variables of adata-based clinical disease profile. It can thus provide a singlemeasurement for an individual's disease activity. In certain embodiment,the disease activity score obtained from individuals of a population isaveraged to obtain a disease activity score for such a population or forspecific segments thereof. For example, the population may beindividuals treated in a particular clinic and the specific segments maybe male or female patients or patients above or below a certain age. Incertain embodiment of the invention, the disease activity may also beassessed via a simple summation of the measurable parameters and/orvariables.

A correlation set is a collection of measurable indicator parametersand/or variables from a relevant number of individuals that forms thebasis to correlate members of said collection to each other and/or to acertain disease, e.g., arteriosclerosis, e.g., via a phenotypicalcorrelation plot. “Correlating” or “to correlate” in this context meansestablishing a link between, e.g., two variables, irrespective ofwhether or not statistically significant. The data set of thecorrelation set is broader of a profiling set an thus allowscorrelating, that is making a connection between of measurable indicatorparameters and/or variables between a connection has previously not ornot clearly been determined.

A population according to the present invention is a group ofindividuals that stem from the same geographical area, which may be acontinent, a country, a state, a city, a town, a district or a buildingsuch as a hospital or a clinic. In a preferred embodiment of the presentinvention, the profiling set and/or correlation set is drawn fromindividuals from one population. The tools and or methods of the presentinvention are, in a preferred embodiment, tied to such a population or asubset thereof. This allows personalized and targeted treatment ofpatients with complex diseases or with a risk to develop them. Theinvention also allows to determine trends of a disease within apopulation.

The invention is, in a preferred embodiment, directed at a comprehensiveclinical data array that describes a common, complex human disease suchas symptomatic arteriosclerosis. In one embodiment, the invention isdirected at accurately determining the individual patient's diseaseactivity using a set of non-invasive, affordable and accessible clinicaltests. In a particularly preferred embodiment of the invention, thepatient's data is compared with a contemporary cohort of patientssuffering from the disease (i.e. symptomatic arteriosclerosis), afeature classical cardiovascular risk calculation tools generally do nothave. The patients who serve as an internal reference group, are, e.g.,living in the same area and they are treated at the same institution.Thus, they are drawn form the same population. This circumstance avoidsthe temporal and spatial bias that may affect the accurate diseaseprediction by most known risk algorithms (6).

Facing the diagnostic break-through of modern imaging technologies inthe late 20^(th) century, clinical examination is becoming an orphanscience among clinicians and particularly among young physicians. In thefollowing, data-based clinical disease profiles, will be discussed usingsymptomatic arteriosclerosis as a non-limiting example. The data-basedclinical disease profile, is, in this embodiment, entirely based onsimple clinical findings such as patient's history, bedside proceduresand a few lab tests. Its strength lies in the detection of theindividual disease activity both for asymptomatic patients withouttreatment but also for patients with fully established secondaryprevention. This individualized assessment forms the basis for thepersonalized treatment of arteriosclerosis. It facilitates focusedtreatment of the system which is most involved in (such as body shape orgeneral inflammation) or most affected by (such as arteries, the heartor the kidney) the disease.

In one preferred embodiment of the invention, the positive predictivevalue of the disease activity score is assessed. For asymptomaticpatients this score correlates with the 10-year risk to developcardiovascular events as calculated by the Framingham algorithm (18),thus suggesting its prognostic significance. Accordingly, in a preferredembodiment of the present invention the disease activity score of anindividual without the respective disease, is used prognosticallyforecasting a disease development and/or onset for about 15 years, about10 years, about 5, years, about 4 years, about 3, years or about 2years. The data-based clinical disease profile and the disease activityscore is, in a preferred embodiment, defined by the same cohort ofpatients for which it sets the reference, that is, its data is drawnfrom the same population as, e.g., the assessed individual. Notably,both single numerical variables and the disease activity score have beenshown reproducible when collected by different investigators duringdifferent time periods. The fact that the disease activity scoreincreases with the severity of arteriosclerosis as assessed by thenumber of organ beds affected by the disease reflects a biologicallyrelevant assessment. Third, age is an important risk factor forcardiovascular events (26) and, not surprisingly, age also affects thedisease activity score. Patients with symptomatic arteriosclerosis showan accelerated progression of arteriosclerosis as measured with thedisease activity score that is revealed after age forty. Although thedisease activity score is significantly higher for symptomatic patients,there is significant overlap with asymptomatic individuals. Additional,comprehensive diagnostic tools such as genomic or transcriptomic testscan, in certain embodiment, be employed to separate the two patientgroups, but also to identify presymptomatic individuals accurately.Finally, the conditions that precipitate the development of symptomaticarteriosclerosis are evolving with time. They may be different invarious regions of the world and are subject to the medical management,be it primary or secondary prevention strategies or access torevascularization procedures. Therefore, this data-based clinicaldisease profile may look different 10 or 20 years from now, it may lookdifferent in the setting of a private practice or in a tertiary carereferral center of a university hospital.

As the person skilled in the art will appreciate, the present approachof assessing a complex disease with bedside, accessible and affordableclinical tests can be adopted for other common conditions such aschronic obstructive pulmonary disease, osteoporosis, even cancer orother conditions as those described elsewhere herein. The comprehensive,unbiased collection of clinical datasets together with an unambiguousassignment of the diagnostic vignette allows to confirm or discoverlinked conditions such as osteoporosis which seems to accompanysymptomatic, but not asymptomatic arteriosclerosis.

The invention will be explained in the following using symptomaticarteriosclerosis as a non-limiting example.

In the context of this example, it was tested whether non-invasive,bedside diagnostic procedures and a set of additional, simple tests thatare usually part of the initial evaluation of a patient are able toidentify individuals with symptomatic arteriosclerosis. In a prospectiveobservational clinical cohort study data was collected that wereobtained by a physician in a standardized clinical exam. A set of morethan 70 numerical variables were systematically compared betweenpatients who suffered from symptomatic arteriosclerosis and patients whohad no cardiovascular events in the past. 25 of these datasets wereclearly different between the two patient groups. The quartiledistribution of these data was the basis of a quantitative scoringsystem which formed the basis for a color coded, data-based clinicaldisease profile of arteriosclerosis. This comprehensive clinicalapproach to describe a complex disease such as symptomaticarteriosclerosis may be the first step to evaluate personalized,targeted treatment strategies for individual patients.

Methods Patient Recruitment

718 in-patients who were treated for any reason at one single ward of adepartment of a Hospital, were screened for exclusion criteria toparticipate in the study. Exclusion criteria that were fulfilled by 40%of the patients were either the inability to give informed consent orterminal illness. Two physicians (C. S., M. M.) were sequentiallyinvolved in the data collection that covered two study periods: period1: 11 months (C. S.), and period 2: 8 months (M. M.). Overall, 431patients without exclusion criteria were personally confronted with thestudy protocol. 269 patients consented to participate. The patients weregrouped in three categories based on the clinical history: group 1—nocardiovascular events in the past; group 2—cardiovascular events in thepast which define symptomatic arteriosclerosis; group 3—symptoms werecompatible with symptomatic arteriosclerosis, but clinical evidence toprove it was lacking. For the data-based clinical disease profile,patients without cardiovascular events (group 1) and patients withproven, symptomatic arteriosclerosis (group 2) were compared (Table 1).Cardiovascular events which defined symptomatic arteriosclerosis in thispatient cohort were a) for coronary heart disease: myocardialinfarction, significant stenosis of coronary arteries as assessed byangiography, angina pectoris with signs of myocardial ischemia, historyof coronary bypass surgery or other revascularization procedures, b) forcerebrovascular disease: ischemic stroke, history of carotid surgery, c)for peripheral arterial occlusive disease: ankle brachial index <0.9(15) and symptoms of claudicatio intermittens, significant stenosis ofarteries and symptoms of claudicatio, history of peripheral bypasssurgery or other revascularization procedure, d) for aorticarteriosclerosis: symptomatic aortic aneurysm, infrarenal diameter >3 cm(16) and e) for arteriosclerosis of the kidney: renal artery stenosis,impaired renal function (17) with normal urine analysis, history ofrenal artery revascularization procedures. Male sex, arterialhypertension, diabetes mellitus, dyslipidemia, smoking and a positivefamily history for cardiovascular disease were the six conventionalcardiovascular risk factors which were assessed based on the clinicalhistory (18).

Comprehensive Clinical Assessment

All participants were subject to a standardized interview (H, history)and examined in a standardized clinical examination (C) (see Appendix Ifor questionaire). The clinical examination started with the patient inthe standing position. Body weight and size, waist and hipcircumference, blood pressure and heart rate were measured on both armsin the standing position first. Thereafter, the examination wascontinued in the supine position. Blood pressure and heart rate measuredin supine position were usually obtained at the end of the examination,together with the determination of the ankle brachial index (ABI). Itwas assessed using bedside doppler ultrasound (Dopplex 5 MHz, HNEHealthcare GmbH, Hilden, Germany). Patients with incompressible legarteries had a formal ABI of more than 1.5 and these excessively highindexes were excluded from the dataset. The patient's record served as asource for additional information such as laboratory tests (L), X-rays(X), electrocardiogram (E), stress test or echocardiogram. For thisaspect, it was a purely observational study. No additional laboratorytesting were performed except what was requested by the treatingphysicians. From the full clinical assessment which was collected in anelectronic data base, 76 numeric variables were selected (seeSupplemental Table 1) for further statistical analysis. 15 (20%) wereobtained from the interview, 19 (25%) from the clinical examination, 33(43%) from the laboratory tests and 9 (12%) from x-ray,electrocardiogram, stress test or echocardiogram. For 15 of these 76parameters, the dataset was incomplete, i.e. information from less than75% of the patients were collected (Appendix II).

Data-Based Clinical Disease Profile and Disease Activity Score

For 61 of the 76 numeric variables, data were available for more than75% of the patients. These datasets were compared between patientswithout cardiovascular events in the past (group 1) and patients withproven symptomatic arteriosclerosis (group 2) using the Mann Whitney Utest (Appendix II). For 25 variables (41%), the P-value was below 0.1and these parameters were selected to be part of the data-based clinicaldisease profile (Table 2). For both groups, the percentile distributionof the data was calculated and the quartile ranges are shown (Table 2).The group of patients with the disease, i.e. with proven symptomaticarteriosclerosis (group 2, n=100 patients) was defining the standardreference for the data-based clinical disease profile. The calculatedquartile ranges served for color coding the patient's individual data(Table 2 and FIG. 1). For most of the numerical variables, patients withsymptomatic arteriosclerosis had higher median values than the patientswithout cardiovascular events. Therefore, lighter gray shading (or greencolor) was assigned to the lowest quartile closest to the asymptomaticpatients, light gray shading (or yellow color) to the second, dark grayshading (or orange color) to the third quartile and darker gray shading(or red color) to the quartile most distant to the asymptomaticpatients. Values below the minimal value were coded as lightest gray andvalues above the maximal value were coded as darkest gray. Exceptions tothis rule were the ankle brachial index, the peripheral heart rate atstanding position, the creatinine clearance and the hemoglobinconcentration. For these 5 parameters, the patients with symptomaticarteriosclerosis had lower median values compared to the asymptomaticpatients, and therefore color coding followed the opposite rule: thehighest quartile range was assigned to the lighter gray shading (orgreen color), the 3rd to the light gray shading (or yellow color), the2^(nd) to the dark gray shading (or orange color) and the lowestquartile range to the darker gray shading (or red color) (FIG. 1).

The Phenotypical Correlation Plot

Correlation profiling is used by physiologists to assess the influenceof genotype on cardiovascular phenotype (19, 20). In a similar way, weused this approach to comprehensively compare the phenotype of patientswith symptomatic arteriosclerosis and patients without cardiovascularevents (FIG. 6). The 61 parameters, for which a complete dataset wasavailable, were correlated linearly with each other and the linearcorrelation coefficient R was calculated. Again, color coding wasapplied to visualize different and opposite degrees of correlation (FIG.6-1, 6-2, legend). Correlation coefficients of 0+/−0.01 are shown inblack, increasingly positive correlations are turning into gray andlight gray, whereas increasingly negative correlations are turning intolight scattered and strong scattered.

Statistical Analysis

All statistical analyses were performed using SPSS version 12.0 (SPSSInc., Chicago Ill., USA). The numeric data which were obtained in thegroup of patients with symptomatic arteriosclerosis were compared to thepatients without cardiovascular events using the Mann-Whitney U test.The presence or absence of cardiovascular risk factors was comparedbetween the two groups using the X²-test. Linear correlationcoefficients were determined by the least squares method andcorrelations were tested for significance using the Spearman's test.P-values <0.05 were supposed to indicate a significant differencebetween the groups.

Receiver Operating Characteristic (Roc) Curve for the Assessment ofDiagnostic Suitability of the Disease Activity Score

The disease activity score for arteriosclerosis was analyzed andcompared to a number of conventional risk factors as well as to theFramingham score as used as diagnostic tool for arteriosclerosis.

Evolution of the Disease Activity Score

The prospective evolution of the disease activity score depending on thestate of the disease was assessed by determining the disease activityscore in a individual in a two year interval.

Results

The Clinical Bedside Examination Identified Patients with SymptomaticArteriosclerosis

Of the 269 patients who participated in this study, 100 (37%) hadsymptomatic arteriosclerosis, i.e. they had suffered from cardiovascularevents in the past. 110 (41%) had no history of cardiovascular eventssuch as myocardial infarction, stroke, intermittent claudication,revascularization procedures or other disease defining conditions (Table1). For 59 (22%) patients, the definite allocation to one of these twogroups was not possible. The characteristics of the patients withoutcardiovascular events in the past and of the patients with provensymptomatic arteriosclerosis are summarized in Table 1. On average,patients with symptomatic arteriosclerosis were older, and allconventional risk factors were significantly more common in this group.Smoking, a positive family history of cardiovascular events and arterialhypertension were the most prevalent risk factors for both patientgroups (Table 1). 60% of the patients with symptomatic arteriosclerosishad coronary heart disease, 26% had cerebrovascular disease, 26%peripheral arterial occlusive disease, 7% aortic and 7% renalarteriosclerosis. For about a quarter of these patients, more than onevascular bed was affected by the disease.

For 15 of the 76 numerical variables tested, the dataset was incomplete(Appendix II) and they were therefore excluded from the furtherstatistical analysis. Of the remaining 61 parameters, 25 (43%) showed aconsistent difference (P-value <0.1 in the Mann-Whitney U test) whenthey were compared between the two patient groups. The majority wasobtained in the bedside examination: 7 (28%) from the interview, 11(44%) from the clinical examination, only 5 (20%) from laboratory testsand 3 (12%) from chest X-ray or electrocardiogram. For these 25variables, the quartile distribution was calculated (Table 2) and thenormalized interquartile limits are shown as color coded columns inFIG. 1. These interquartile limits define the range for color coding ofthe individual patient's data: depending on the value for age, number ofpack years, number of children etc which are displayed as a white circle(FIG. 1), either green, yellow, orange or red color is assigned to thevariable. The color coded values obtained for the 25 variables are thenused for the calculation of the disease activity score: a green valueadds 0, a yellow value 1, an orange value 2 and a red value 3 points.The sum is divided by the total number of variables assessed which isideally 25 (FIG. 1). Therefore, the scale for the score ranges from aminimal value of 0 to a maximal value of 3. Each of the 25 variablescontributes one 25^(th) part of the score value. Accordingly, in thisexample, the formula to calculate the disease activity score isΣ[α₁+α₂+α₃+ . . . +α₂₅]/(25-[missing variables].

Reproducibility of the Data-Based Clinical Disease Profile

Since 18 of the 25 variables which contributed to the disease activityscore were obtained by a physician during the clinical examination andtherefore could be subject to interobserver variability, it was testedwhether two independent observers would obtain similar results duringtwo consecutive study periods. During the first period lasting 11 monthsand during the second period, lasting 8 months, the median values forthe 75 numeric variables showed on average excellent correlation (FIG.2A). When the variables were compared during the two study periods usingnon-parametric tests, only four parameters showed a significantdifference in the group of symptomatic patients: the hemoglobinconcentration, the monocyte count and the waist and hip circumference(Appendix III). In contrast, for the patients who did not suffer fromcardiovascular events, 16 variables were different between the two studyperiods. This suggests that a more heterogeneous collection of diseasesin this second group could explain the more pronounced diversity ofclinical findings. This observation gives additional support forchoosing the symptomatic patients to set the reference for thedata-based clinical disease profile and for the disease activity score.The percentile distribution of the disease activity score was alsocalculated between the two study periods (FIG. 2B). It showed areproducible, normal distribution when it was obtained from differentpatients and by different investigators.

The Data-Based Clinical Disease Profile: a Rational Basis for theIndividual Assessment and Classification of Arteriosclerosis

Most of the 25 variables which were significantly different in thissystematic and comprehensive comparison of clinical information fromsymptomatic and asymptomatic patients reflect important clinical signsof arteriosclerosis: the anthropometric data reveal abdominal obesity(21), the elevated systolic blood pressure (22) and the reduced anklebrachial index (15) are the consequence of reduced wall compliance andstenotic arteries, cardiomegaly identifies left ventricular hypertrophy(23), QT prolongation may correlate with electric vulnerability (3),diminished creatinin clearance and glucosuria reflect kidney injury(17). Anemia, monocytosis and elevated blood sedimentation rate aresigns of chronic inflammation (24) and finally, the high number of drugsand repetitive hospitalizations are health economic aspects ofsymptomatic arteriosclerosis (FIG. 1). These categories which emergedfrom the data analysis have immediate implications for the individualclassification of the disease. For example, the male patient whose dataare shown in FIG. 1 (white circles) had a myocardial infarction threeyears ago. His disease profile is drawing the physician's attention toabdominal obesity as the only remaining, clinically apparent sign of thedisease under combined anti-hypertensive and lipid lowering treatment.

When the color coded disease profiles obtained from each individualpatient are aligned in an array format (FIG. 3) the patient cohort canbe divided into the following four groups: female patients withoutcardiovascular events (upper left quadrant), female patients withsymptomatic arteriosclerosis (upper right quadrant), male patientswithout cardiovascular events (lower left quadrant) and male patientswith symptomatic arteriosclerosis (lower right quadrant). Within thequadrants, the data-based clinical disease profile is shown first and itis followed by the disease activity score. The conventional risk factorsidentified by gray boxes are shown next, and the sum of risk factorswhich are normalized to the symptomatic patients are shown in a colorcoded, visually weighed manner. Within each of the four groups, thepatients are sorted according to their disease activity score. For theasymptomatic patients, this sorting strategy reveals a cluster of bothfemale and male patients with the metabolic syndrome (FIG. 2, brackets):they have abdominal obesity, elevated systolic blood pressure and oftendiabetes (25). For the symptomatic patients shown on the right panel,this clustering of the metabolic syndrome is less evident. However, thearray of the symptomatic patients reveals a gender-specific, distinctprofile of the disease: whereas the female patients, despite of takingthe same number of drugs, have on average higher, uncontrolled systolicblood pressure (145 (125-160) mmHg versus 130 (115-148) mmHg, P=0.02)the male patients are rather obese having a higher body mass index (27.7(24.6-30.7) kg/m² versus 25.4 (23.3-28.1) kg/m², P=0.04 and a higherwaist hip ratio (1.02 (1.0-1.07) versus 0.91 (0.88-0.97), P<0.001) thanfemale patients.

The Data-Based Disease Activity Score Correlates with the 10-Year Riskfor Cardiovascular Events, with the Severity of the Disease and withAge.

For 40 of the 110 patients without cardiovascular events the dataset wascomplete to calculate the Framingham risk score (ref). This wastranslated into the 10-year risk to suffer from cardiovascular events.This 10-year risk showed a weak but significant correlation with thedisease activity score (FIG. 4A). Furthermore, patients with extensivearteriosclerosis which affects more than one vascular bed had asignificantly higher disease activity score than patients who had onlyone organ involved or patients without cardiovascular events in the past(FIG. 4B). Finally, the disease activity score is significantlycorrelated with age for both asymptomatic and symptomatic patients (FIG.5). However, the rate of progression of the disease with time asidentified by the linear curve fit of the disease score with thepatient's age is faster in symptomatic patients (FIG. 5). For thepatients older than 70 years, the disease activity score was significanthigher in the symptomatic than in the asymptomatic group (1.65(1.33-1.84) versus 1.23 (1.05-1.53), P<0.001).

The Phenotypical Correlation Plot is a Tool to Identify Other ConditionsLinked with Symptomatic Arteriosclerosis.

The phenotypical correlation plots for the asymptomatic (FIG. 6A) andsymptomatic (FIG. 6B) patients reveal a good association between theanthropometric data and the blood pressure measurements, for both groupsof patients. Within the symptomatic patients, body height was negativelycorrelated with age and with all the four systolic blood pressuremeasurements (FIG. 6B, insert, arrows) whereas in patients withoutcardiovascular events, there was no obvious or consistently negativecorrelation observed. This unexpected finding could be translated intothe concept (FIG. 7) that symptomatic arteriosclerosis is linked withosteoporosis (as measured by an age dependent decrease in body size),and that for an individual patient with symptomatic arteriosclerosis, asmaller size is linked to stiffening and loss of compliance of thearterial wall (as measured by an elevated systolic blood pressure).

The Receiver Operating Characteristic (ROC) Curve for the AssessmentShows that The Disease Activity Score is Highly Suitable for theAssessment of Disease Activity

As can be seen from FIGS. 8 and 9, the area under the curve is 0.688 forthe Framingham score, 0.756 for the number of risk factors in theindividuals and 0.839 for the disease activity score.

The Disease Activity Score Increases Significantly Over Time inIndividuals with the Disease but not in Individuals without the DiseaseIt was tested how the disease activity score evolves prospectively inpatients suffering from symptomatic arteriosclerosis compared toindividuals free of cardiovascular events.

It was demonstrate that within two years, the disease activity scoresincreases significantly in patients with symptomatic arteriosclerosisbut not in individuals without active disease FIG. 10. The significancetest used to determine the difference between disease activity scoreduring visit 1 and visit 2 was the Wilcoxon test.

TABLE 1 Patient characteristics No cardiovascular Symptomatic eventsarteriosclerosis (n = 110) (n = 100) P-values^(#) Cardiovascular riskfactors n (%) Male sex 51 (46.4) 57 (57) 0.095 Age (years) 56.00 72.00<0.001 Body mass index (kg/M²) 25.6  26.40 0.085 Arterial hypertension40 (36.4) 67 (67) <0.001 Diabetes mellitus 12 (10.9) 30 (30) 0.005Dyslipidemia 9 (8.2) 50 (50) <0.001 Smoking 57 (51.8) 61 (61) 0.017Family history of cardiovascular disease 48 (43.6) 61 (61) 0.038 Drugsat examination n (%) Antiplatetelet drugs 7 (6.4) 69 (69) <0.001Anticoagulants 27 (24.6) 36 (36) 0.07 Nitrates 1 (0.9) 18 (18) <0.001Betablockers 19 (17.3) 60 (60) <0.001 Diuretics 17 (15.5) 48 (48) <0.001ACE inhibitors 14 (12.7) 56 (56) <0.001 Angiotensin II receptor blockers8 (7.3) 11 (11) 0.347 Ca²⁺ channel blockers 7 (6.4) 26 (26) <0.001 Oralglucose-lowering agents 9 (8.2) 14 (14) 0.178 Insulin 5 (4.6) 21 (21)<0.001 Statins 14 (12.7) 68 (68) <0.001 Other drugs 5 (4.6) 8 (8) 0.299Cardiovascular events defining symptomatic arteriosclerosis % Coronaryheart disease — 60 Myocardial infarction — 49 Significant stenosis ofcoronary arteries (angiographic — 23 findings) Angina pectoris withsigns of myocardial ischemia — 9 (e.g. exercise testing) History ofrevascularization — 14 Cerebrovascular disease — 26 Ischemic stroke — 26Peripheral arterial occlusive disease — 27 Ankle-brachial-index < 0.9and symptoms of claudicatio — 14 intermittens Angiographically provenand symptoms of claudicatio — 5 intermittens History ofrevascularization — 17 Arteriosclerosis of the aorta — 7Arteriosclerosis of the kidney — 11 Number of organs affected bycardiovascular events    1 — 72    2 — 26 ≧3 — 2 ^(#)The two patientgroups were compared using the Mann-Whitney-U-Test (for numerical data)or the X²-test (for non-numerical data)

TABLE 2 The numerical data selected for the data-based clinical diseaseprofile and the disease activity score No cardiovascular eventsSymptomatic atherosclerosis (n = 110) (n = 100) Maxi- Mini- Maxi- Mini-mum 75. 25. mum mum 75. 25. mum P- Parameter Method^(§) value percentileMedian Percentile value value percentile Median percentile value value#Age (years) H 88.0 67.75 56.0 46.25 18.0 92.0 76.0 72.0 66.75 39.0<0.001 Smoking (packyears) H 150.0 25.0 1.0 0.0 0 150.0 50.0 15.0 0.00.0 0.018 Number of children H 7.0 2.0 2.0 1.0 0 6.0 3.0 2.0 1.0 0.00.028 Body mass index (kg/m²) C 40.1 27.75 25.6 23.25 14.5 42.40 29.7326.4 24.07 16.59 0.085 Waist circumference (cm) C 120.0 101.0 95.0 82.056.0 140.0 109.0 99.5 90.0 71.0 0.006 Hip circumference (cm) C 126.0105.0 100.0 91.0 71.0 124.0 110.0 101.5 94.0 78.0 0.078 Waist hip ratioC 1.20 1.00 0.94 0.88 0.75 1.20 1.04 1.00 0.91 0.78 0.006 Systolic bloodpressure left C 180.0 140.0 130.0 110.0 85.0 195.0 160.0 140.0 120.090.0 0.003 arm supine (mmHg) Systolic blood pressure C 190.0 140.0 130.0110.0 90.0 200.0 160.0 135.0 120.0 85.0 0.005 right arm supine (mmHg)Systolic blood pressure left C 180.0 140.0 120.0 100.0 80.0 225.0 155.0130.0 120.0 80.0 0.001 arm standing (mmHg) Systolic blood pressure C200.0 140.0 120.0 110.0 80.0 190.0 150.0 130.0 120.0 80.0 0.007 rightarm standing (mmHg) Heart diameter (cm) X 17.7 14.9 13.5 12.5 9.40 19.816.6 15.6 13.9 11.3 <0.001 Heart lung ratio X 0.61 0.49 0.47 0.43 0.350.71 0.56 0.51 0.48 0.38 <0.001 Ankle brachial index right* C 1.46 1.241.14 1.06 0.76 1.50 1.15 1.00 0.95 0.42 <0.001 Ankle brachial indexleft* C 1.45 1.21 1.15 1.07 0.70 1.50 1.13 1.02 0.86 0.43 <0.001 QT time(sec) E 0.50 0.40 0.37 0.35 0.27 0.55 0.43 0.40 0.37 0.21 <0.001Peripheral heart rate C 120.0 92.0 80.0 72.0 48.0 160.0 88.0 78.0 68.044.0 0.02 standing (bpm) Creatinin clearance L 242.2 137.1 103.8 79.516.91 158.1 93.3 72.4 54.6 15.2 <0.001 (mL/min per 1.73 m²) Glucosuria L1.0 0.0 0.0 0.0 0.0 3.0 0.0 0.0 0.0 0.0 0.003 (negative = 0, + = 1, ++ =2, +++ = 3) Hemoglobin (g/dL) L 17.1 14.4 13.6 12.0 5.7 16.3 14.0 12.611.2 8.4 0.011 Monocytes (10⁹/L) L 3.41 0.87 0.47 0.29 0.05 2.78 0.860.59 0.40 0.00 0.079 Blood sedimentation rate L 105.0 27.5 10.0 4.0 2.0114.0 31.5 13.0 6.0 1.0 0.086 (mm/h) Number of drugs H 10.0 4.0 2.0 1.00 14.0 8.0 6.0 4.0 0.0 <0.001 (on admission) Number of medication O 11.05.0 4.0 2.0 0 14.0 9.0 7.0 5.0 2.0 <0.001 (current) Number of admissionsto H 8.0 1.0 0.0 0.0 0 15.0 3.0 1.0 0.0 0.0 0.002 this hospital Diseaseactivity score O 1.83 1.22 0.92 0.67 0.25 2.67 1.79 1.49 1.27 0.41<0.001 *Patients (7 without cardiovascular events, 6 with symptomaticatherosclerosis) who had incompressible ankle arteries (=ABI > 1.5) wereexcluded from this analysis. #The numeric data obtained during the twostudy periods were compared using Mann-Whitney-U-Test. ^(§)Method bywhich the data was obtained: H = history, C = clinical examination, L =laboratory test, X = chest X-ray, E = electrocardiography, O = others.

Once give the disclosure provided herein, many features, modifications,and improvements will become apparent to the skilled artisan. Suchfeatures, modifications, and improvements are therefore considered partof the present invention.

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APPENDIX I General questionnaire for databased clinical diseaseprofiling number area question data type default multiple choice 1.1.1personal patient id number empty space 1.1.2 data hospital patient idtext empty space 1.1.3 date of examination date 00.00.0000 1.1.4 date ofbirth date 00.00.0000 1.1.5 last name text empty space 1.1.6 first nametext empty space 1.1.7 address text empty space 1.1.8 phone number textempty space 1.1.9 cell phone text empty space 1.1.10 fax number textempty space 1.1.11 e-mail text empty space 1.1.12 professional status(last) text empty space 1.1.13 retired yes/no not assessed yes, no1.1.14 since when? date 00.00.0000 1.1.15 family physician text emptyspace 1.1.16 health insurance text empty space 1.1.17 insurance classmultiple choice, not assessed simple 1.1.18 additional comments textempty space 1.1.19 history of date of first hospitalization in date00.00.0000 hospitalizations the current hospital 1.1.20 date of firsthospitalization in date 00.00.0000 the department of medicine 1.1.21last hospitalization in the date 00.00.0000 department of medicine1.1.22 total number of hospitalizations number empty space 1.1.23 numberof hospitalizations in number empty space the department of medicine1.1.24 type of current hospitalization multiple choice, empty spaceemergency, regular admission simple 1.1.25 admitted by multiple choice,empty space family physician, emergency simple physician, ambulance,other hospital, others 1.1.26 admitted to the department of multiplechoice, empty space depends on local setting simple 1.1.27 current wardmultiple choice, empty space depends on local setting simple 1.1.28 dateof current hospitalization date 00.00.0000 1.1.29 date of discharge date00.00.0000 1.1.30 out-patient visit yes/no empty space yes, no 1.1.31additional comments text empty space 1.1.32 Current reason for thecurrent text empty space history hospitalization 1.1.33 additionalcomments text empty space 1.1.34 Personal former diseases yes/no emptyspace yes, no; if no, forward to 1.1.42 1.1.35 history date of the eventdate 00.00.0000 1.1.36 type of event multiple choice, empty spacetonsillectomy, appendectomy, simple cholezysstectomy, hysterectomy,birth of child, myocardial infarction, stroke, thrombosis, pulmonaryembolism, pneumonia, transurethral resection of the prostate, urinarytract infection, arterial hypertension, diabetes, freetext 1.1.37treating physician text empty space 1.1.38 report for the event multiplechoice, empty space no, yes simple 1.1.39 additional comments text emptyspace 1.1.40 additional events? yes/no empty space yes, no; if yes, backto 1.1.36 1.1.41 System's weakness, fatigue multiple choice, empty spacenone, freetext overview simple 1.1.42 appetite multiple choice, emptyspace normal, reduced, increased, simple freetext 1.1.43 thirst multiplechoice, empty space normal, reduced, increased, simple freetext 1.1.44body weight multiple choice, empty space stable, decreasing, increasing,simple freetext 1.1.45 urination multiple choice, empty space normal,dysuria, pollakisuria, simple hematuria, incontinence, freetext 1.1.46bowel movements multiple choice, empty space normal, diarrhea,constipation, simple freetext 1.1.47 nausea multiple choice, empty spacenormal, freetext simple 1.1.48 vomiting multiple choice, empty spacenormal, freetext simple 1.1.49 dyspnea multiple choice, empty spacenormal, NYHA 1, 2, 3, 4 simple 1.1.50 coughing multiple choice, emptyspace normal, freetext simple 1.1.51 expectoration multiple choice,empty space none, hemoptoe, freetext simple 1.1.52 angina pectorismultiple choice, empty space none, NYHA 1, 2, 3, 4 simple 1.1.53 edemamultiple choice, empty space none, feet, ankle, legs, simple anasarka,freetext 1.1.54 blood pression multiple choice, empty space normal,elevated, low, freetext simple 1.1.55 headache multiple choice, emptyspace normal, freetext simple 1.1.56 sleep multiple choice, empty spacenormal, freetext simple 1.1.57 sweating multiple choice, empty spacenormal, freetext simple 1.1.58 veneral disease multiple choice, emptyspace none, freetext simple 1.1.59 pregnancies number empty space 1.1.60births number empty space 1.1.61 menstruation date 00.00.0000 1.1.62menarche date 00.00.0000 1.1.63 anticonception multiple choice, emptyspace simple 1.1.64 vaccinations multiple choice, empty space simple1.1.65 alcohol multiple choice, empty space simple 1.1.66 smokingmultiple choice, empty space simple 1.1.67 allergies multiple choice,empty space simple 1.1.68 drugs multiple choice, empty space simple1.1.69 illicit drugs multiple choice, empty space simple 1.1.70additional comments text empty space 1.1.71 Social maritial statusmultiple choice, empty space history simple 1.1.72 children number emptyspace 1.1.73 profession text empty space 1.1.74 retired since date00.00.0000 1.1.75 hobbies text empty space 1.1.76 military serviceyes/no empty space yes, no 1.1.77 pets multiple choice, empty spacenone, freetext simple 1.1.78 travel history multiple choice, empty spacefreetext simple 1.1.79 dependency multiple choice, empty space freetextsimple 1.1.80 living condition text empty space 1.1.81 additionalcomments text empty space Family history 1.2.1 parents father multiplechoice, empty space healthy, sick, died, unknown; if simple unknown goto 1.2.7 1.2.2 date of birth, father date 00.00.0000 1.2.3 date ofdeath, father date 00.00.0000 1.2.4 cause of death, father text emptyspace 1.2.5 diseases, father multiple choice, empty space diabetes,obesity, multiple hypertension, tuberculosis, asthma, allergies, cancer,rheumatoid diseases, mental illness, epilepsy, others 1.2.6 additionalcomments, father text empty space 1.2.7 mother multiple choice, emptyspace healthy, sick, died, unknown; if simple unknown go to 1.2.13 1.2.8date of birth, mother date 00.00.0000 1.2.9 date of death, mother date00.00.0000 1.2.10 cause of death, mother text empty space 1.2.11diseases, mother multiple choice, empty space healthy, cardiovascularevents, multiple diabetes, obesity, hypertension, tuberculosis, asthma,allergies, cancer, rheumatoid diseases, mental illness, epilepsy, others1.2.12 additional comments, mother text empty space 1.2.13 siblingssiblings yes/no empty space yes, no; if no, go to question 1.2.23 1.2.14number number empty space 1.2.15 1st sibling multiple choice, emptyspace brother, sister, freetext simple 1.2.16 health state multiplechoice, empty space healthy, sick, died, unknown simple 1.2.17 date ofbirth, sibling date 00.00.0000 1.2.18 date of death, sibling date00.00.0000 1.2.19 cause of death, sibling text empty space 1.2.20diseases multiple choice, empty space healthy, cardiovascular events,multiple diabetes, obesity, hypertension, tuberculosis, asthma,allergies, cancer, rheumatoid diseases, mental illness, epilepsy, others1.2.21 additional comments, sibblings text empty space 1.2.22 additionalsibblings yes/no empty space yes, no; if yes, go to 1.2.15: 2nd sibling.if no, go to 1.2.23 1.2.23 children children yes/no empty space yes, no;if no, go to 1.2.33 1.2.24 number of children number empty space 1.2.251st child multiple choice, empty space son, daughter simple 1.2.26health state multiple choice, empty space health, sick, died, unknownsimple 1.2.27 date of birth, child date 00.00.0000 1.2.28 date of death,child date 00.00.0000 1.2.29 cause of death, child text empty space1.2.30 diseases multiple choice, empty space healthy, cardiovascularevents, multiple diabetes, obesity, hypertension, tuberculosis, asthma,allergies, cancer, rheumatoid diseases, mental illness, epilepsy, others1.2.31 additional comment, child text empty space 1.2.32 additionalchildren yes/no empty space yes, no; if yes, go to 1.2.25: 2nd child ifno, go to 1.2.33 1.2.33 comments additional comments text empty spacephysical examination organ number system question data type unit defaultmultiple choice 2.1.1 vital sign temperatur peripheral number ° C. emptyspace 2.1.2 temperatur rectal number ° C. empty space 2.1.3 bloodpressure left, supine number mmHg empty space systolic 2.1.4 bloodpressure left, supine number mmHg empty space diastolic 2.1.5 bloodpressure left, standing number mmHg empty space systolic 2.1.6 bloodpressure left, standing, number mmHg empty space diastolic 2.1.7 pulsequality multiple choice, empty space normal, durus, celer, altus,multiple tardus, parvus, alternans, paradoxux, freetext 2.1.8 pulse,left supine number bpm empty space 2.1.9 pulse, left standing number bpmempty space 2.1.10 blood pressure right supine number mmHg empty spacesystolic 2.1.11 blood pressure right supine number mmHg empty spacediastolic 2.1.12 blood pressure right standing number mmHg empty spacesystolic 2.1.13 blood pressure right standing, number mmHg empty spacediastolic 2.1.14 pulse quality multiple choice, empty space normal,durus, celer, altus, simple tardus, parvus, alternans, paradoxux,freetext 2.1.15 pulse, right supine number bpm empty space 2.1.16 pulse,right standing number bpm empty space 2.1.17 respiration number bpmempty space 2.1.18 general appearance multiple choice, empty space well,acutely ill, compromised, simple severely ill, cirtically ill, freetext2.1.19 orientation multiple choice, empty space fully oriented,desoriented for multiple time, desoriented for place, desoriented forperson, hallucinations, obsessions, recent memory impaired, remotememory impaired, freetext 2.1.20 mental state multiple choice, emptyspace normal, depressive, anxious, simple emotionally labile, freetext2.1.21 speech multiple choice, empty space normal, fluent, aphasia,simple dysarthria, freetext 2.1.22 nutritional state multiple choice,empty space normal, obese, cachectic, simple freetext 2.1.23 bodymultiple choice, empty space normal, athletic, pycnic, simpleleptosomal, freetext 2.1.24 other comments text empty space 2.1.25 emptyspace 2.1.26 anthropometry age number years empty space calculated (fromdate of birth and current date) 2.1.27 gender multiple choice, emptyspace male, female, freetext simple 2.1.28 ethnic origin multiplechoice, empty space caucasian, mediterranean, simple asia, africa, southamerica, freetext 2.1.29 body weight number kg empty space 2.1.30 sizenumber m empty space 2.1.31 body mass index number kg/m2 empty spacecalculated 2.1.32 waist circumference number cm empty space 2.1.33 hipcircumference number cm empty space 2.1.34 waist hip ratio number emptyspace calculated 2.1.35 other comments text empty space 2.1.36 skincolor, pigmentation multiple choice, empty space normal, dark, black,red, multiple icteric, pale, freetext 2.1.37 teleangiectasies yes/noempty space if no, go to 2.1.39 2.1.38 localization multiple choice,empty space generalized, head, neck, trunc, multiple left arm, rightarm, left leg, right leg, freetext 2.1.39 lipid storage lesions yes/noempty space if no, go to 2.1.42 2.1.40 type multiple choice, empty spacexanthelasma, xanthoma, multiple freetext 2.1.41 localization multiplechoice, empty space generalized, head, neck, trunc, multiple left arm,right arm, left leg, right leg, freetext 2.1.42 exanthema yes/no emptyspace if no, go to 2.1.47 2.1.43 primary lesion multiple chocice, emptyspace none, urticaria, macula, multiple papula, plaque, knods, bulla,vesicle, pustule, scales, freetext 2.1.44 localization multiple choice,empty space generalized, head, neck, trunc, multiple left arm, rightarm, left leg, right leg, freetext 2.1.45 secondary lesion multiplechocice, empty space none, crusts, erosion, multiple excoriation, ulcer,scar, freetext 2.1.46 localization multiple choice, empty spacegeneralized, head, neck, trunc, multiple left arm, right arm, left leg,right leg, freetext 2.1.47 hematoma multiple choice, empty space none,petechia, ekchymosis, multiple purpura, freetext 2.1.48 localizationmultiple choice, empty space generalized, head, neck, trunc, multipleleft arm, right arm, left leg, right leg, freetext 2.1.49 benign tumorsmultiple choice, empty space none, naevi, fibroma, verruca multiplesenilis, neurofibroma, freetext 2.1.50 localization multiple choice,empty space generalized, head, neck, trunc, multiple left arm, rightarm, left leg, right leg, freetext 2.1.51 malignant tumors multiplechoice, empty space none, actinic hyperkeratosis, multiple spinalioma,basalioma, melanoma, Kaposi sarcoma, freetext 2.1.52 localizationmultiple choice, empty space generalized, head, neck, trunc, multipleleft arm, right arm, left leg, right leg, freetext 2.1.53 primary hairmultiple choice, empty space normal, alopecia, abdominal multiplebaldnesss, hypertrichosis, freetext 2.1.54 secondary hair multiplechoice, empty space normal, male hairtype, female multiple hairtype,hirsutism, freetext 2.1.55 nails multiple choice, empty space normal,leukonychia, white multiple bands, onychomykosis, splinter hemorrhages,shallow pitting, freetext 2.1.56 hidrosis multiple choice, empty spacenormal, hyperhidrosis, dry multiple skin, freetext 2.1.57 breast leftmultiple choice, empty space normal, atrophic, enlarged, multiplenodule, inverted nipple, peaud' orange, freetext 2.1.58 breast rightmultiple choice, empty space normal, atrophic, enlarged, multiplenodule, inverted nipple, peaud' orange, freetext 2.1.59 scars yes/noempty space if no, go to 2.1.62 2.1.60 number number empty space 2.1.61localization text empty space 2.1.62 implants multiple choice, emptyspace none, port-a-cath, pacemaker, multiple defibrillator, artificialjoint, freetext 2.1.63 other comments text empty space 2.1.64musculosceletal vertebral column multiple choice, empty space normal,kyphosis, lordosis, system simple skoliosis, freetext 2.1.65 Schobernumber empty space 2.1.66 Ott number empty space 2.1.67 painful areasyes/no empty space 2.1.68 localization multiple choice, empty spacecervical vertebral column, multiple thoracic vertebral column, lumbalvertebral column, sacrum, freetext 2.1.69 joints multiple choice, emptyspace normal, abnormal, freetext simple 2.1.70 localization multiplechoice, empty space left shoulder, right shoulder, multiple left elbow,right ellbow, left carporadial, right carporadial, left carpoulnar,right carpoulnar, left carpophalangeal, right carpophalageal, leftproximal interphalangeal, right proximal interphalangeal, left distalinterphalangeal, right distal interphalangeal, left hip, right hip, leftknee, right knee, left ankle, right ankle, left tarsophalangeal, righttarsophalangeal, left interphalangeal, right interphalangeal, freetext2.1.71 mobility multiple choice, empty space normal hypermobile,limited, simple freetext 2.1.72 localization multiple choice, emptyspace left shoulder, right shoulder, multiple left elbow, right ellbow,left carporadial, right carporadial, left carpoulnar, right carpoulnar,left carpophalangeal, right carpophalageal, left proximalinterphalangeal, right proximal interphalangeal, left distalinterphalangeal, right distal interphalangeal, left hip, right hip, leftknee, right knee, left ankle, right ankle, left tarsophalangeal, righttarsophalangeal, left interphalangeal, right interphalangeal, freetext2.1.73 effusion yes/no empty space if no, go to 2.1.75 2.1.74localization multiple choice, empty space left shoulder, right shoulder,multiple left elbow, right ellbow, left carporadial, right carporadial,left carpoulnar, right carpoulnar, left carpophalangeal, rightcarpophalageal, left proximal interphalangeal, right proximalinterphalangeal, left distal interphalangeal, right distalinterphalangeal, left hip, right hip, left knee, right knee, left ankle,right ankle, left tarsophalangeal, right tarsophalangeal, leftinterphalangeal, right interphalangeal, freetext 2.1.75 inflammationyes/no empty space if no, go to 2.1.77 2.1.76 localization multiplechoice, empty space left shoulder, right shoulder, multiple left elbow,right ellbow, left carporadial, right carporadial, left carpoulnar,right carpoulnar, left carpophalangeal, right carpophalageal, leftproximal interphalangeal, right proximal interphalangeal, left distalinterphalangeal, right distal interphalangeal, left hip, right hip, leftknee, right knee, left ankle, right ankle, left tarsophalangeal, righttarsophalangeal, left interphalangeal, right interphalangeal, freetext2.1.77 deformation yes/no empty space if no, go to 2.1.79 2.1.78localization multiple choice, empty space left shoulder, right shoulder,multiple left elbow, right ellbow, left carporadial, right carporadial,left carpoulnar, right carpoulnar, left carpophalangeal, rightcarpophalageal, left proximal interphalangeal, right proximalinterphalangeal, left distal interphalangeal, right distalinterphalangeal, left hip, right hip, left knee, right knee, left ankle,right ankle, left tarsophalangeal, right tarsophalangeal, leftinterphalangeal, right interphalangeal, freetext 2.1.79 other commentstext empty space 2.1.80 legs edema yes/no empty space 2.1.81 varicosismultiple choice, empty space none, port wine stains left, port multiplewine stains right, branch varicosis left, branch varicosis right, truncvaricosis left, trunc varicosis right, freetext 2.1.82 other commentstext empty space 2.1.83 lymph multiple choice, empty space normal,enlarged, painful, nodes multiple immobile, freetext 2.1.84 localizationmultiple choice, empty space generalized, cervical left, multiplecervical right, axillary left, axillary right, supraclavicular left,supraclavicular right, inguinal left, inguinal right, freetext 2.1.85consistency multiple choice, empty space soft, solid, stony,fluctuating, multiple freetext 2.1.86 other comments text empty space2.1.87 head meningism yes/no empty space 2.1.88 face motion multiplechoice, empty space normal, hypomimia, amimia, multiple tick, freetext2.1.89 face muscles multiple choice, empty space normal, facial paresisleft, multiple facial paresis right, freetext 2.1.90 eyes multiplechoice, empty space normal, diminished visual multiple acuity left,diminished visual acuity right, left bulbus painful, right bulbuspainful, left bulbus rockhard, right bulbus rockhard, exophthalmusright, exophthalmus left, freetext 2.1.91 lids multiple choice, emptyspace normal, ptosis left, ptosis right, multiple freetext 2.1.92conjunctiva multiple choice, empty space normal, red left, red right,multiple freetext 2.1.93 sklera multiple choice, empty space normal,icteric left, icteric right, multiple blue left, blue right, freetext2.1.94 cornea multiple choice, empty space normal, opacity left, opacitymultiple right, freetext 2.1.95 lenses multiple choice, empty spacenormal, cataract left, cataract multiple right, artificial lens left,artificial lens right, freetext 2.1.96 visual field multiple choice,empty space normal, hemianopsia left, multiple hemianopsia right,bitemporal hemianopsia, freetext 2.1.97 bulbus motion multiple choice,empty space normal, convergent strabism, multiple divergent strabism,conjugated gaze palsy, freetext. 2.1.98 nystagmus (fast component toyes/no empty space left) 2.1.99 nystagmus (fast component to yes/noempty space right) 2.1.100 pupil left multiple choice, empty spacenormal, miotic, mydriatic, multiple freetext 2.1.101 pupil rightmultiple choice, empty space normal, miotic, mydriatic, multiplefreetext 2.1.102 pupil motion light left multiple choice, empty spacenormal, weak, absent, freetext multiple 2.1.103 pupil motion light rightmultiple choice, empty space normal, weak, absent, freetext multiple2.1.104 pupil motion convergence left multiple choice, empty spacenormal, weak, absent, freetext multiple 2.1.105 pupil motion convergenceright multiple choice, empty space normal, weak, absent, freetextmultiple 2.1.106 eyes fundus left multiple choice, empty space normal,arteriovenous multiple crossings, cotton wool, bleedings, hardexsudates,swollen disk, freetext 2.1.107 eyes fundus right multiple choice, emptyspace normal, arteriovenous multiple crossings, cotton wool, bleedings,hardexsudates, swollen disk, freetext 2.1.108 nose multiple choice,empty space normal, rhinophym, freetext multiple 2.1.109 nose breathingmultiple choice, empty space normal, obstruction left, multipleobstruction right, freetext 2.1.110 lips multiple choice, empty spacenormal, cyanotic, strawberry multiple red, perleche, freetext 2.1.111teeth multiple choice, empty space normal, healthy, loose, multiplemissing, prosthesis, erosions, sensitivity, freetext 2.1.112 gumsmultiple choice, empty space normal, hypertrophic, atrophic, multipleinflamed, freetext 2.1.113 tongue multiple choice, empty space normal,atrophic, strawberry multiple tongue, glossitis, macroglossia, whitepatches, freetext 2.1.114 mucus membrane multiple choice, empty spacenormal, ulcers, xerostomia, multiple koplik spots, freetext 2.1.115palate multiple choice, empty space normal, red, white patches, multiplefreetext 2.1.116 gag reflex multiple choice, empty space normal,decreased, absent, multiple increased, freetext 2.1.117 tonsils multiplechoice, empty space normal, enlarged, red, stipples, multiple purlulent,state after tonsilectomy, freetext 2.1.118 foetor multiple choice, emptyspace normal, ethylic, nicotinic, multiple uremic, hepatic, anaerobic,freetext 2.1.119 hearing multiple choice, empty space normal, reduced,missing, multiple Weber to left, Weber to right, Rinne abnormal left,Rinne abnormal right, freetext 2.1.120 other comments text empty space2.1.121 cervical thyroid multiple choice, empty space normal, homogenousgoiter multiple nodular goiter, freetext 2.1.122 other comments textempty space 2.1.123 cardio- peripheral circulation multiple choice,empty space normal, cold skin, warm skin, vascular multiple freetext2.1.124 cyanosis multiple choice, empty space none, central, akral,freetext multiple 2.1.125 edema multiple choice, empty space none,generalized, face, legs, multiple left leg, right leg, freetext 2.1.126jugular veins multiple choice, empty space normal, distended, Kussmaulmultiple sign, underfilled, freetext 2.1.127 hepatojugular refluxnegative/positive empty space 2.1.128 vein pulsations yes/no empty space2.1.129 other comments text empty space 2.1.130 left apical impulsemultiple choice, empty space normal, enlarged point of multiple maximalimpulse, prolonged, lateral displacement, freetext 2.1.131 right apicalimpulse multiple choice, empty space absent, present simple 2.1.132rhythm multiple choice, empty space regular, extrasystoles, multipleabsolute arrhythmia, freetext 2.1.133 systolic murmur yes/no empty spaceif no, go to 2.1.139 2.1.134 intensity multiple choice, empty space 1/6,2/6, 3/6, 4/6, 5/6, 6/6 multiple 2.1.135 maximal intensity multiplechoice, empty space 2nd ICS parasternal right, 2nd multiple ICSparasternal left, Erb, PMI, freetext 2.1.136 quality multiple choice,empty space pure, coarse, rumbling, low multiple pitched, mediumpitched, high pitched, freetext 2.1.137 duration multiple choice, emptyspace early, late, holosystolic, multiple freetext 2.1.138 transmissionmultiple choice, empty space carotids, axilla, freetext multiple 2.1.139diastolic murmur yes/no empty space if no, go to 2.1.2.1.144 2.1.140maximal intensity multiple choice, empty space 2nd ICS parasternalright, 2nd multiple ICS parasternal left, Erb, PMI, freetext 2.1.141quality multiple choice, empty space pure, coarse, rumbling, lowmultiple pitched, medium pitched, high pitched, freetext 2.1.142duration multiple choice, empty space early, late, holodiastolic,multiple freetext 2.1.143 transmission multiple choice, empty spacecarotid, axilla, freetext multiple 2.1.144 S1 multiple choice, emptyspace normal, accentuated, split, multiple freetext 2.1.145 S2 multiplechoice, empty space normal, accentuated, split, multiple freetext2.1.146 S3 yes/no empty space 2.1.147 S4 yes/no empty space 2.1.148right temporal artery multiple choice, empty space normal, weak,painful, absent, multiple freetext 2.1.149 left temporal artery multiplechoice, empty space normal, weak, painful, absent, multiple freetext2.1.150 right carotid artery multiple choice, empty space normal, weak,absent, bruit, multiple freetext 2.1.151 left carotid artery multiplechoice, empty space normal, weak, absent, bruit, multiple freetext2.1.152 right radial artery multiple choice, empty space normal, weak,absent, bruit, multiple freetext 2.1.153 left radial artery multiplechoice, empty space normal, weak, absent, bruit, multiple freetext2.1.154 right femoral artery multiple choice, empty space normal, weak,absent, bruit, multiple freetext 2.1.155 left femoral artery multiplechoice, empty space normal, weak, absent, bruit, multiple freetext2.1.156 right popliteal artery multiple choice, empty space normal,weak, absent, bruit, multiple freetext 2.1.157 left popliteal arterymultiple choice, empty space normal, weak, absent, bruit, multiplefreetext 2.1.158 right tibial posterior artery multiple choice, emptyspace normal, weak, absent, bruit, multiple freetext 2.1.159 left tibialposterior artery multiple choice, empty space normal, weak, absent,bruit, multiple freetext 2.1.160 right tibial anterior artery multiplechoice, empty space normal, weak, absent, bruit, multiple freetext2.1.161 left tibial anterior artery multiple choice, empty space normal,weak, absent, bruit, multiple freetext 2.1.162 aorta multiple choice,empty space normal, enlarged, bruit, multiple freetext 2.1.163 vascularbruits yes/no empty space if no, go to 2.1.165 2.1.164 localization textempty space 2.1.165 ABI resting left number empty space 2.1.166 ABIresting right number empty space 2.1.167 ABI stress left number emptyspace 2.1.168 ABI stress right number empty space 2.1.169 other commentstext empty space 2.1.170 thorax&lungs form multiple choice, empty spacenormal, barrel shape, pectus multiple carinatum, pectus excavatum,freetext 2.1.171 respiratory motion multiple choice, empty spacesymmetric, asymmetric, multiple freetext 2.1.172 periodicity ofrespiration multiple choice, empty space normal, Kussmaul, Cheynemultiple Stokes, Biot, apnea, freetext 2.1.173 fremitus left yes/noempty space 2.1.174 fremitus right yes/no empty space 2.1.175 whisperedvoice left yes/no empty space 2.1.176 whispered voice right yes/no emptyspace 2.1.177 palpation left multiple choice, empty space normal,freetext simple 2.1.178 palpation right multiple choice, empty spacenormal, freetext simple 2.1.179 percussion left multiple choice, emptyspace normal, hypersonoric, dull, simple freetext 2.1.180 percussionright multiple choice, empty space normal, hypersonoric, dull, simplefreetext 2.1.181 auscultation left multiple choice, empty space normal,vesicular, tubular, multiple wheezes, rales, stridor, pleural rub,freetext 2.1.182 localization multiple choice, empty space upperventral, mid ventral, multiple lower ventral, upper dorsal, mid dorsal,lower dorsal 2.1.183 auscultation right multiple choice, empty spacenormal, vesicular, tubular, multiple wheezes, rales, stridor, pleuralrub, freetext 2.1.184 localization multiple choice, empty space upperventral, mid ventral, multiple lower ventral, upper dorsal, mid dorsal,lower dorsal 2.1.185 other comments text empty space 2.1.186 abdomentenderness multiple choice, empty space normal, tender, abnormal,multiple freetext 2.1.187 localization multiple choice, empty space leftupper quadrant, left lower multiple quadrant, right upper quadrant,right lower quadrant 2.1.188 resistence multiple choice, empty spacenone, guarding, induced multiple guarding, rebound tenderness, referredrebound tenderness, tumor, freetext 2.1.189 localization multiplechoice, empty space left upper quadrant, left lower multiple quadrant,right upper quadrant, right lower quadrant 2.1.190 maximal intensitymultiple choice, empty space left upper quadrant, left lower multiplequadrant, right upper quadrant, right lower quadrant 2.1.191 ascitesmultiple choice, empty space none, possible, sure simple 2.1.192 bowelsounds multiple choice, empty space normal, high pitched, absent,multiple increased, bruits, freetext 2.1.193 liver number cm in emptyspace MCL 2.1.194 liver (scratch) number cm in empty space MCL 2.1.195liver consistency multiple choice, empty space normal, solid, rockhard,multiple nodular, painful, freetext 2.1.196 spleen multiple choice,empty space absent, freetext multiple 2.1.197 kidney left multiplechoice, empty space normal, painful, freetext multiple 2.1.197 kidneyright multiple choice, empty space normal, painful, freetext multiple2.1.198 hernias multiple choice, empty space normal, hernia right,hernia multiple left, freetext 2.1.199 genital organs multiple choice,empty space normal, hydrocele right, multiple hydrocele left, freetext2.1.200 urinary catheter yes/no empty space 2.1.201 rectal multiplechoice, empty space normal, hemorrhoids, marisks, multiple polyps,freetext 2.1.202 prostate multiple choice, empty space normal, solid,painful, multiple enlarged, rockhard, fluctuating, freetext 2.1.203Courvoisier sign yes/no 2.1.204 Mc Burney sign yes/no 2.1.205 Psoas signleft yes/no 2.1.206 Psoas sign right yes/no 2.1.207 other comments textempty space 2.1.208 nervous odor multiple choice, empty space normal,absent, freetext system multiple 2.1.209 corneal reflex multiple choice,empty space normal, absent right, absent simple left, freetext 2.1.210palate multiple choice, empty space symmetric, palsy right, palsy simpleleft, freetext 2.1.211 swallowing multiple choice, empty space normal,freetext simple 2.1.212 trunc motion multiple choice, empty spacenormal, freetext simple 2.1.213 trunc sensibility multiple choice, emptyspace simple 2.1.214 upper extremity, right, tonus multiple choice,empty space normal, reduced, flaccid, rigor, simple spasm, freetext2.1.215 upper extremity, right, strength multiple choice, empty space M5(normal), M4, M3, M2, M1, simple M0, freetext 2.1.216 upper extremity,right, position multiple choice, empty space normal, signe du cinquiemesimple doigt, main creuse, paresis, palsy, freetext 2.1.217 upperextremity, right, multiple choice, empty space normal,dysdiadochokinesis, diadochokinesis simple adiadochoinesis, freetext2.1.218 upper extremity, right, finger to multiple choice, empty spacenormal, dysmetric, freetext nose simple 2.1.219 upper extremity, right,touch multiple choice, empty space normal, reduced, freetext simple2.1.220 upper extremity, right, pain multiple choice, empty spacenormal, reduced, freetext simple 2.1.221 upper extremity, right,multiple choice, empty space normal, reduced, freetext temperaturesimple 2.1.222 upper extremity, right, vibration multiple choice, emptyspace normal, reduced, freetext simple 2.1.223 upper extremity, left,tonus multiple choice, empty space normal, reduced, flaccid, rigor,simple spasm, freetext 2.1.224 upper extremity, left, strength multiplechoice, empty space MS (normal), M4, M3, M2, M1, simple M0, freetext2.1.225 upper extremity, left, position multiple choice, empty spacenormal, signe du cinquieme simple doigt, main creuse, paresis, palsy,freetext 2.1.226 upper extremity, left, multiple choice, empty spacenormal, dysdiadochokinesis, diadochokinese simple adiadochoinesis,freetext 2.1.227 upper extremity, left, finger to multiple choice, emptyspace normal, dysmetric, freetext nose simple 2.1.228 upper extremity,left, touch multiple choice, empty space normal, reduced, freetextsimple 2.1.229 upper extremity, left, pain multiple choice, empty spacenormal, reduced, freetext simple 2.1.230 upper extremity, left, multiplechoice, empty space normal, reduced, freetext temperature simple 2.1.231upper extremity, left, vibration multiple choice, empty space normal,reduced, freetext simple 2.1.232 lower extremity, right, tonus multiplechoice, empty space normal, reduced, flaccid, rigor, simple spasm,freetext 2.1.233 lower extremity, right, strength multiple choice, emptyspace M5 (normal), M4, M3, M2, M1, simple M0, freetext 2.1.234 lowerextremity, right, position multiple choice, empty space normal, paresis,palsy, freetext simple 2.1.235 lower extremity, right, multiple choice,empty space normal, dysdiadochokinesis, diadochokinesis simpleadiadochoinesis, freetext 2.1.236 lower extremity, right, heel tomultiple choice, empty space normal, dysmetric, freetext knee simple2.1.237 lower extremity, right, Lasègue negative/positive empty space2.1.238 angle number ° empty space 2.1.239 lower extremity, right,inverted negative/positive empty space Lasègue 2.1.240 lower extremity,right, touch multiple choice, empty space normal, reduced, freetextsimple 2.1.241 lower extremity, right, pain multiple choice, empty spacenormal, reduced, freetext simple 2.1.242 lower extremity, right,multiple choice, empty space normal, reduced, freetext temperaturesimple 2.1.243 lower extremity, right, vibration multiple choice, emptyspace normal, reduced, freetext simple 2.1.244 lower extremity, left,tonus multiple choice, empty space normal, reduced, flaccid, rigor,simple spasm, freetext 2.1.245 lower extremity, left, strengt multiplechoice, empty space M5 (normal), M4, M3, M2, M1, simple M0, freetext2.1.246 lower extremity, left, position multiple choice, empty spacenormal, paresis, palsy, freetext simple 2.1.247 lower extremity, left,multiple choice, empty space normal, dysdiadochokinesis, diadochokinesissimple adiadochoinesis, freetext 2.1.248 xtremity, left, heel to kneemultiple choice, empty space normal, dysmetric, freetext simple 2.1.249lower extremity, left, Lasègue negative/positive empty space 2.1.250angle number ° empty space 2.1.251 lower extremity, left, invertednegative/positive empty space Lasègue 2.1.252 lower extremity, left,touch multiple choice, empty space normal, reduced, freetext simple2.1.253 lower extremity, left, pain multiple choice, empty space normal,reduced, freetext simple 2.1.254 lower extremity, left, multiple choice,empty space normal, reduced, freetext temperature simple 2.1.255 lowerextremity, left, vibration multiple choice, empty space normal, reduced,freetext simple 2.1.256 Romberg multiple choice, empty space normal,drop to left, drop to simple right, undirected dropping, freetext2.1.257 gait multiple choice, empty space normal, small steps, wide-simple based, steppage, freetext 2.1.258 limping multiple choice, emptyspace normal, Duchenne left, simple Duchenne right, Trendelenburg left,Trendelenburg right, freetext 2.1.259 Unterberg test multiple choice,empty space normal, rotating to left, rotating simple to right, freetext2.1.260 biceps (C6) right multiple choice, empty space normal, absent,missing, simple hyperactive, freetext 2.1.261 biceps (C6) left multiplechoice, empty space normal, absent, missing, simple hyperactive,freetext 2.1.262 triceps (C7) right multiple choice, empty space normal,absent, missing, simple hyperactive, freetext 2.1.263 triceps (C7) leftmultiple choice, empty space normal, absent, missing, simplehyperactive, freetext 2.1.264 Knips/Trömner right negative/positiveempty space 2.1.265 Knips/Trömner left negative/positive empty space2.1.266 abdominal right multiple choice, empty space normal, absent,missing, simple hyperactive, freetext 2.1.267 abdominal left multiplechoice, empty space normal, absent, missing, simple hyperactive,freetext 2.1.268 knee (L4) right multiple choice, empty space normal,absent, missing, simple hyperactive, freetext 2.1.269 knee (L4) leftmultiple choice, empty space normal, absent, missing, simplehyperactive, freetext 2.1.270 ankle (S1) right multiple choice, emptyspace normal, absent, missing, simple hyperactive, freetext 2.1.271ankle (S1) left multiple choice, empty space normal, absent, missing,simple hyperactive, freetext 2.1.272 babinski right negative/positiveempty space 2.1.273 babinski left negative/positive empty space

APPENDIX II Numerical variables obtained from the patients. SymptomaticNo cardiovascular events arteriosclerosis Code (total 110 patients)(total 100 patients) number Parameter Method^(§) Median n (%) Median n(%) P-value^(#) I Age (years) H 56.00 110 (100) 72.00 100 (100) <0.001II Weight (kg) C 72.30 109 (99.1) 75.35 98 (98) 0.385 III Height (m) C1.67 103 (93.6) 1.68 89 (89) 0.754 IV Body mass index¹ (kg/m²) C 25.60103 (93.6) 26.40 88 (88) 0.0085 V Waist circumference² (cm) C 95.00 97(88.2) 99.50 84 (84) 0.006 VI Hip circumference² (cm) C 100.00 97 (88.2)101.50 84 (84) 0.078 VII Waist hip ratio² C 0.94 97 (88.2) 1.00 84 (84)0.006 VIII Systolic blood pressure left C 130.00 108 (98.2) 140.00 97(97) 0.001 arm supine (mmHg) IX Diastolic blood pressure left C 80.00108 (98.2) 80.00 97 (97) 0.421 arm supine (mmHg) X Systolic bloodpressure right C 130.00 109 (99.1) 135.00 95 (95) 0.005 arm supine(mmHg) XI Diastolic blood pressure right C 80.00 109 (99.1) 80.00 95(95) 0.717 arm supine (mmHg) XII Peripheral heart rate C 76.00 109(99.1) 72.00 100 (100) 0.124 supine (bpm) XIII Systolic blood pressureleft C 120.00 101 (91.8) 130.00 79 (79) <0.001 arm standing (mmHg) XIVDiastolic blood pressure left C 80.00 101 (91.8) 80.00 79 (79) 0.464 armstanding (mmHg) XV Systolic blood pressure right C 120.00 100 (90.9)130.00 78 (78) 0.007 arm standing (mmHg) XVI Diastolic blood pressureright C 80.00 101 (91.8) 80.00 78 (78) 0.761 arm standing (mmHg) XVIIPeripheral heart rate C 80.00 102 (92.7) 78.00 82 (82) 0.02 standing(bpm) XVIII Central heart rate C 76.00 109 (99.1) 72.00 100 (100) 0.311supine (bpm) XIX Ankle brachial index right* C 1.14 95 (86.4) 1.00 80(80) <0.001 XX Ankle brachial index left* C 1.15 86 (78.2) 1.02 78 (78)<0.001 XXI Hemoglobin (g/dL) L 13.60 110 (100) 12.55 100 (100) 0.011XXII Leukocytes (10⁹/L) L 8.50 109 (99.1) 8.30 100 (100) 0.896 XXIIIThrombocytes (10⁹/L) L 253.00 109 (99.1) 259.00 100 (100) 0.738 XXIVNeutrophile granulocytes L 5.61 94 (85.5) 5.66 90 (90) 0.991 (10⁹/L) XXVEosinophilic granulocytes L 0.07 96 (87.3) 0.12 91 (91) 0.077 (10⁹/L)XXVI Basophilic granulocytes L 0.04 96 (87.3) 0.03 90 (90) 0.756 (10⁹/L)XXVII Lymphocytes (10⁹/L) L 1.70 96 (87.3) 1.60 91 (91) 0.256 XXVIIIMonocytes (10⁹/L) L 0.47 96 (87.3) 0.59 89 (89) 0.079 XXIX HbA1c (%) L6.10 18 (16.4) 7.10 33 (33) XXX Blood glucose level after L 6.20 79(71.8) 6.00 73 (73) overnight fast (mmol/L) XXXI Cholesterol total(mmol/L) L 5.00 45 (41) 4.60 68 (68) XXXII LDL cholesterol (mmol/L) L3.28 42 (38.2) 2.65 62 (63) XXXIII HDL cholesterol (mmol/L) L 1.08 44(40) 1.05 67 (67) XXXIV Triglycerides (mmol/L) L 1.10 43 (39.1) 1.60 60(60) XXXV Kreatinin (μmol/L L 62.00 107 (97.3) 77.00 100 (100) <0.001XXXVI Body surface area (m²) L 1.84 103 (93.6) 1.87 89 (89) 0.577 XXXVIIKreatinin clearance L 103.80 100 (90.9) 72.40 89 (89) <0.001 (mL/min per1.73 m²) XXXVIII Blood sedimentation rate L 10.00 79 (71.8) 13.00 80(80) 0.086 (mm/h) XXXIX C-reactive protein (mg/L) L 7.00 104 (94.6) 9.0097 (97) 0.534 XL Creatine kinase (U/L) L 98.50 84 (76.4) 107.00 86 (86)0.217 XLI Creatin kinase, MB form L 4.00 25 (22.7) 6.00 52 (52) (U/L)XLII Troponin I (ng/mL) L 0.02 26 (23.6) 0.04 43 (43) XLIII GOT/ASAT(U/L) L 23.00 104 (94.6) 25.00 95 (95) 0.272 XLIV GPT/ALAT (U/L) L 24.00104 (94.6) 23.00 95 (95) 0.903 XLV Alkaline phosphatase (U/L) L 67.00 99(90) 77.00 88 (88) 0.197 XLVI Gamma glutamyl L 41.00 43 (39.1) 61.50 34(34) transpeptidase GGT (U/L) XLVII D-dimer (μg/L) L 1.03 23 (20.9) 2.0211 (11) XLVIII Brain natriuretic peptide L 256.50 6 (5.5) 220.00 17 (17)(pg/mL) XLIX Thyroidea stimulating L 1.12 36 (32.7) 1.47 41 (41) hormone(mU/L) L INR L 1.10 107 (97.3) 1.10 92 (92) 0.316 LI Proteinuria L 0.00110 (100) 0.00 100 (100) 0.23 (negative = 0, + = 1, ++ = 2, +++ = 3) LIIGlucosuria L 0.00 110 (100) 0.00 100 (100) 0.003 (negative = 0, + = 1,++ = 2, +++ = 3) LIII Urine leukocytosis L 0.00 110 (100) 0.00 100 (100)0.647 (negative = 0, + = 1, ++ = 2, +++ = 3) LIV Heart rate in ECG (bpm)E 77.00 98 (89.1) 73.00 93 (93) 0.187 LV QT time (sec) E 0.37 95 (86.4)0.40 90 (90) <0.001 LVI Sokolov index right E 0.30 96 (87.3) 0.40 92(92) 0.494 ventricle (mV) LVII Sokolov index left E 1.70 97 (88.2) 1.6092 (92) 0.514 ventricle (mV) LVIII Maximal exercise capacity O 137.50 10(9.1) 100.00 9 (9) stress test (W) LIX Lung diameter (cm) X 28.55 70(63.6) 29.60 77 (77) 0.35 LX Heart diameter (cm) X 13.50 70 (63.6) 15.6077 (77) <0.001 LXI Heart lung ratio X 0.47 70 (63.6) 0.51 77 (77) <0.001LXII Left ventricular ejection O 40.50 14 (12.7) 40.00 37 (37) fraction(%) LXIII Age father at time of death H 73.00 71 (64.6) 74.00 78 (78)0.09 (years) LXIV Age mother at time of death H 80.00 54 (49.1) 80.00 76(76) 0.88 (years) LXV Number of siblings H 2.00 87 (88.2) 2.00 86 (86)0.693 LXVI Number of children H 2.00 110 (100) 2.00 100 (100) 0.028LXVII Number of drugs (on H 2.00 110 (100) 6.00 100 (100) <0.001admission) LXVIII Number of drugs for the H 0.00 110 (100) 3.50 100(100) <0.001 treatment of atherosclerosis (on admission) LXIX Number ofdrugs (current) O 4.00 110 (100) 7.00 100 (100) <0.001 LXX Number ofdrugs for the O 0.00 110 (100) 4.00 100 (100) <0.001 treatment ofathersclerosis (current) LXXI Number of admissions to this H 0.00 108(98.2) 1.00 96 (96) 0.002 hospital LXXII Packyears H 1.00 110 (100)15.00 100 (100) 0.018 LXXIII Number of standard alcoholic H 0.00 110(100) 0.00 100 (100) 0.127 drinks LXXIV If female: age at menarch H14.00 55 (91.7 of 13.25 40 (93.0 of 0.873 (years) female femalepatients) patients) LXXV If female: age at menopause H 48.00 29 (48.3 of50.00 35 (81.4 of 0.354 (years) female female patients) patients) LXXVINumber of cardiovascular H 2.00 110 (100) 3.00 100 (100) <0.001 riskfactors LXXVII Disease activity score O 0.92 110 (100) 1.51 100 (100)<0.001 ^(#)The data of the patient groups are shown as median values.The two patient groups were compared by Mann-Whitney-U-Test. Data setswith P < 0.1 were selected for the disease activity score. *Patients (7without cardiovascular events, 6 with symptomatic arteriosclerosis) whohad incompressible ankle arteries (=ABI > 1.5) were excluded from thisanalysis. ^(§)Method by which the data was obtained: H = history, C =clinical examination, L = laboratory test, X = chest X-ray, E =electrocardiography, O = others.

APPENDIX III Test for the reproducibility of the clinical dataacquisition. Values with <75% completion of dataset are excluded fromthis analysis⁺ No cardiovascular Symptomatic Events (n = 110)arteriosclerosis (n = 100) Median Median Median Median Code numberParameter Method^(§) (1st period) (2nd period) P-value^(#) (1st period)(2nd period) P-value^(#) XXI Hemoglobin (g/dL) L 13.70 13.20 0.144 13.6512.25 0.002 V Waist circumference (cm) C 97.00 87.50 0.020 105.00 95.000.003 VI Hip circumference (cm) C 102.00 91.00 <0.001 104.00 98.00 0.007XXVIII Monocytes (10⁹/L) L 0.42 0.64 0.002 0.51 0.70 0.012 VII Waist hipratio C 0.94 0.95 0.717 1.00 0.97 0.069 XLIII GOT/ASAT (U/L) L 23.0024.00 0.847 23.00 26.00 0.102 XVIII Central heart rate supine (bpm) C76.00 76.00 0.794 72.00 76.00 0.117 XVII Peripheral heart rate standing(bpm) C 80.00 84.00 0.303 72.00 80.00 0.123 LI Proteinuria L 0.00 0.000.863 0.00 0.00 0.153 (negative = 0, + = 1, ++ = 2, +++ = 3) XXXVIIIBlood sedimentation rate (mm/h) L 10.00 8.50 0.482 11.00 15.00 0.175XXXV Kreatinin (μmol/L) L 66.50 56.00 0.023 73.00 79.00 0.206 XVIDiastolic blood pressure right arm C 80.00 80.00 0.148 75.00 80.00 0.213standing (mmHg) XV Systolic blood pressure right arm C 120.00 125.000.231 120.00 130.00 0.219 standing (mmHg) LIX Lung diameter (cm) X 28.6028.75 0.262 28.80 30.05 0.230 XXIII Thrombocytes (10⁹/L) L 233.50 282.000.029 267.00 252.50 0.241 LXVII Number of drugs (on admission) H 3.001.00 0.006 5.00 6.00 0.243 LXI Heart lung ratio X 0.47 0.47 0.634 0.520.50 0.252 LXXV If female: age at menopause (years) H 43.00 53.00 0.04653.00 50.00 0.254 XIII Systolic blood pressure left arm C 120.00 122.500.424 130.00 130.00 0.267 standing (mmHg) XXVII Lymphocytes (10⁹/L) L1.60 2.00 0.057 1.65 1.50 0.271 XII Peripheral heart rate supine (bpm) C76.00 72.00 0.985 70.00 72.00 0.273 LVII Sokolov index left ventricle(mV) E 1.80 1.50 0.311 1.45 1.70 0.278 LXXI Number of admissions to thishospital H 0.00 0.00 0.055 1.00 1.00 0.280 III Height (m) C 1.67 1.670.970 1.69 1.67 0.282 XI Diastolic blood pressure right arm C 80.0080.00 0.411 80.00 80.00 0.309 supine (mmHg) I Age (years) H 58.00 51.000.018 73.50 72.00 0.317 LXXIII Number of standard alcoholic drinks H0.00 0.00 0.991 0.75 0.00 0.347 XXVI Basophilic granulocytes (10⁹/L) L0.03 0.05 0.019 0.03 0.04 0.383 XLV Alkaline phosphatase (U/L) L 67.0068.00 0.907 77.00 78.00 0.395 LXIII Age father at time of death (years)H 74.00 74.50 0.756 73.00 72.00 0.430 LXIX Number of drugs (current) O4.00 3.00 0.040 6.00 7.00 0.435 XXXIX C-reactive protein (mg/L) L 4.0034.00 0.001 8.00 16.00 0.443 LXV Number of siblings H 2.00 2.00 0.6723.00 3.00 0.460 XXXVII Kreatinin clearance L 91.12 122.00 0.009 73.8570.54 0.533 (mL/min per 1.73 m²) LXIV Age mother at time of death(years) H 80.00 87.00 0.643 82.00 78.00 0.542 LII Glucosuria L 0.00 0.000.711 0.00 0.00 0.550 (negative = 0, + = 1, ++ = 2, +++ = 3) XXXVI Bodysurface area (m²) C 1.85 1.81 0.826 1.87 1.86 0.568 XL Creatine kinase(U/L) L 98.50 96.00 0.784 99.00 111.00 0.593 LXVI Number of children H2.00 2.00 0.554 2.00 2.00 0.619 LXX Number of drugs for the treatment ofO 1.00 0.00 0.001 4.00 4.50 0.641 atherosclerosis (current) LVI Sokolovindex right ventricle (mV) E 0.40 0.30 0.924 0.40 0.40 0.652 II Weight(kg) C 73.35 70.10 0.678 75.00 75.70 0.665 LX Heart diameter (cm) X13.55 13.20 0.726 15.60 15.55 0.669 XIX Ankle brachial index right* C1.14 1.14 0.957 1.07 1.00 0.681 LXXVI Number of cardiovascular riskfactors H 2.00 2.00 0.939 3.00 3.00 0.698 XX Ankle brachial index left*C 1.16 1.14 0.349 1.05 1.00 0.710 LIV Heart rate in ECG (bpm) E 77.0077.00 0.658 78.00 72.00 0.720 XXIV Neutrophile granulocytes (10⁹/L) L4.54 7.10 0.020 5.23 6.15 0.746 LXXIV If female: age at menarch (years)H 14.00 14.00 0.624 13.00 13.50 0.757 LIII Urine leukocytosis L 0.000.00 0.501 0.00 0.00 0.762 (negative = 0, + = 1, ++ = 2, +++ = 3) XIVDiastolic blood pressure left arm C 80.00 82.50 0.099 80.00 80.00 0.765standing (mmHg) XXII Leukocytes (10⁹/L) L 7.30 9.70 0.023 8.25 8.400.800 LXVIII Number of drugs for the treatment of H 1.00 0.00 0.001 3.004.00 0.806 atherosclerosis (on admission) XLIV GPT/ALAT (U/L) L 23.0025.00 0.218 23.00 22.50 0.816 LV QT time (sec) E 0.38 0.37 0.973 0.400.40 0.818 L INR L 1.10 1.00 0.002 1.10 1.10 0.824 IX Diastolic bloodpressure left arm C 80.00 80.00 0.654 80.00 80.00 0.868 supine (mmHg)XXV Eosinophilic granulocytes (10⁹/L) L 0.07 0.09 0.222 0.13 0.09 0.907X Systolic blood pressure right arm C 130.00 125.00 0.731 140.00 135.000.931 supine (mmHg) IV Body mass index (kg/m²) C 25.68 25.40 0.959 26.2026.76 0.933 VIII Systolic blood pressure left arm C 125.00 130.00 0.790140.00 140.00 0.951 supine (mmHg) LXXVII Disease activity score O 1.000.88 0.132 1.49 1.50 0.981 LXXII Packyears H 0.00 3.00 0.817 15.00 10.000.996 ⁺Numeric data sorted by P-value for patients with symptomaticarteriosclerosis (low → high). *Patients (7 without cardiovascularevents, 6 with symptomatic arteriosclerosis) who had incompressibleankle arteries (=ABI > 1.5) were excluded from this analysis. ^(#)Thenumeric data obtained during the two study periods were compared usingMann-Whitney-U-Test. ^(§)Method by which the data was obtained: H =history, C = clinical examination, L = laboratory test, X = chest X-ray,E = electrocardiography, O = others.

1-23. (canceled)
 24. A method for a data-based clinical disease profileassessment of a disease comprising: providing a database comprising aplurality of data records, wherein each data record comprises a numberof measurable indicator parameters either being in a first set whereinthe data are collected from a first group of individuals having saiddisease; or being in a second set wherein the data are collected from asecond group of individuals without said disease; comparing said firstset of data with said second set of data for each measurable indicatorparameter; and selecting a profiling set for said disease activity as asub record of said measurable indicator parameters including any of saidmeasurable indicator parameters for which the comparison results in astatistically significant difference between data for said measurableindicator parameter from the first set and the second set.
 25. Themethod according to claim 24, wherein selecting comprises use of acorrelation set, correlating at least two different of said measurableindicator parameters of the correlation set.
 26. The method according toclaim 24, comprising calculating the percentile distribution of eachmeasurable indicator parameter of said profiling set for representationas color, shade or value coding reflecting this percentile distribution.27. The method according to claim 26, wherein said coding is based onpercentile ranges such as fertile, quartile, quintile, sextile, septile,octile or nonile ranges of said percentile distribution.
 28. The methodaccording to claims 26, wherein said first group serves as a standardreference.
 29. The method according to claim 24, wherein the selectingstep comprises selecting said profiling set from parameters having aP-value of less than 0.5 in a statistical test comparing two groups suchas a Mann Whitney U test, a student t-test, or a χ2 test when comparisontakes place.
 30. The method according to claim 29, wherein the upperboundary of the P-value is taken from the group comprising 0.4, 0.3,0.2, 0.1, 0.05, 0.025, 0.01, 0.005, 0.0025 and 0.001.
 31. The methodaccording to claim 24, wherein selecting data sets from the first setand the second set for the sub record of said measurable indicatorparameters is restricted to data sets which were collected approximatelywithin the last 5 years, 4 years, 3 years, 2 years, 1 year, 9 months, 6months, 3 months, 2 months, 1 months, 2 weeks, 1 week, 5 days, 2 days or24 hours.
 32. The method according to claim 24, wherein selecting datasets from the first set and the second set for the sub record of saidmeasurable indicator parameters is restricted to data sets wherein thegroups of individuals of the two groups stem from the same population.33. The method according to claim 24, further comprising thedetermination of at least one activity score for at least one disease inan individual comprising measuring the measurable indicator parametersof the profiling set in said individual and determining the activityscore of said disease in said individual.
 34. The method of claim 33,wherein said activity score(s) is/are established in an individual andin said population over time in predetermined time intervals to assesschanges in said population for said disease over time.
 35. The method ofclaim 34, wherein the predetermined time intervals are chosen from thegroup comprising every 3 month, every six month, every year or everyother year.
 36. The method of claim 34, further comprising correlatingthe changes within said activity score(s) to environmental differencebetween points in time at which said activity score(s) is/areestablished.
 37. The method according to claim 34, further comprisingcorrelating said measurable indicator parameters of a correlation set;and determining positive and/or negative correlations between differentof said indicator parameters.
 38. The method according to claim 24,further comprising the determination of at least one activity score forat least one disease in a population comprising measuring the measurableindicator parameters of the profiling set for said population anddetermining said activity score of said disease in said population froman average of the sum of said profiling set.
 39. The method of claim 38,wherein said activity score(s) is/are established in said populationover time in predetermined time intervals to assess changes in saidpopulation for said disease over time.
 40. The method of claim 39,wherein the predetermined time intervals are chosen from the groupcomprising every 3 month, every six month, every year or every otheryear.
 41. The method of claim 38, further comprising correlating thechanges within said activity score(s) to environmental differencebetween points in time at which said activity score(s) is/areestablished.
 42. The method according to claim 38, further comprisingcorrelating said measurable indicator parameters of a correlation set;and determining positive and/or negative correlations between differentof said indicator parameters.
 43. The method according to claim 24,wherein said condition and/or disease is arteriosclerosis, chronicobstructive pulmonary disease, asthma, severe bacterial infectionsincluding pneumonia, sepsis, meningitis, endocarditis, and acute orchronic viral infections, osteoporosis, an autoimmune disease,osteoarthrosis, heart failure, drug dependency, alcoholism, an allergy,cancer, diabetes mellitus Type 2 and metabolic syndrome, arterialhypertension, obesity, smoking, venous thrombosis or pulmonary embolism.44. The method according to claim 24, wherein the measurable indicatorparameters of the profiling set are selected from a group comprisingmyocardial infarction, significant stenosis of coronary arteries asassessed by angiography, angina pectoris with signs of myocardialischemia, history of coronary bypass surgery, ischemic stroke, historyof carotid surgery, ankle brachial index <0.9, symptoms of claudicatiointermittens, significant stenosis of arteries and symptoms ofclaudicatio, history of peripheral bypass surgery, symptomatic aorticaneurysm, infrarenal diameter >3 cm, renal artery stenosis, impairedrenal function with normal urine analysis, history of renal arteryrevascularization procedures, male sex, arterial hypertension, diabetesmellitus, dyslipidemia, smoking and positive family history forcardiovascular disease.